Table 2.
Primary, Secondary and Exploratory Efficacy Outcomes Analyses.
| Change (Baseline - Week 12) (95% CI) | Treatment Effect Difference (95% CI) | Effect Size (d)1 | P value | ||
|---|---|---|---|---|---|
| Lithium | Placebo | ||||
| Primary Outcome | |||||
| NPI agitation/aggression | 3.2 (1.7 to 4.6) | 2.5 (1.1 to 4.0) | 0.7 (−1.4 to 2.7) | 0.23 | t(66)=0.63, 0.53 |
| Secondary Outcome | |||||
| Proportion of Responders n (%)2 | 12/38 (31.6) | 7/39 (17.9) | 2.11 (0.73 to 6.13)2 | - | χ2(1)=1.26, 0.26 |
| Exploratory Efficacy Outcomes | |||||
| CGI Behavior Change n (%)2 | 12/38 (31.6) | 8/39 (20.5) | 1.79 (0.64–5.04)2 | - | χ2(1)=1.33, 0.25 |
| CGI Global Change n (%) | 10/38 (36.8) | 0/39 (15.4) | NA4 | - | <0.0013 |
| NPI total | 14.1 (6.1 to 22.1) | 8.8 (0.8 to 16.7) | 5.3 (−5.6 to 16.4) | 0.34 | t(65)=0.95, 0.35 |
| NPI psychosis | 3.4 (1.3 to 5.5) | 1.5 (−0.6 to 3.6) | 1.9 (−1.0 to 4.8) | 0.48 | t(62)=1.31, 0.20 |
| NPI core score | 6.6 (3.5 to 9.7) | 4.1 (1.0 to 7.2) | 2.5 (−1.8 to 6.8) | 0.41 | t(64)=1.14, 0.26 |
| NPI Hallucinations | 1.0 (0.1 to 1.9) | 1.3 (0.5 to 2.2) | −0.4 (−1.6 to 0.8) | −0.21 | t(60)=−0.59,0.56 |
| NPI Delusions | 2.4 (0.9 to 4.0) | 0.2 (−1.4 to 1.7) | 2.3 (0.2 to 4.4) | 0.76 | t(63)=2.11,0.04 |
| NPI Depression | 0.6 (−0.4 to 1.5) | 0.1 (−0.8 to 1.1) | 0.5 (−0.8 to 1.8) | 0.26 | t(63)=0.72,0.48 |
| NPI Anxiety | 1.7 (0.3 to 3.1) | 2.0 (0.6 to 3.5) | −0.3 (−2.3 to 1.6) | −0.12 | t(65)=−0.33,0.75 |
| NPI Elation | 0.2 (−0.1 to 0.5) | 0.1 (−0.2 to 0.4) | 0.1 (−0.3 to 0.5) | 0.18 | t(58)=0.49,0.63 |
| NPI Disinhibition | −0.3 (−1.2 to 0.5) | 0.3(−0.6 to 1.2) | −0.7 (−1.9 to 0.6) | −0.38 | t(60)=−1.04,0.30 |
| NPI Irritability/lability | 3.0 (1.4 to 4.7) | 0.7 (−0.9 to 2.3) | 2.3 (0.1 to 4.6) | 0.72 | t(67)=2.03,0.05 |
| NPI aberrant motor behavior | 0.8 (−0.4 to 2.0) | 0.6 (−0.6 to 1.8) | 0.2 (−1.5 to 1.8) | 0.09 | t(60)=0.24,0.81 |
| NPI apathy | 0.1 (−1.3 to 1.5) | 0.7 (−0.8 to 2.07) | −0.6 (−2.5 to 1.4) | −0.21 | t(64)=−0.59,0.56 |
| NPI nighttime behaviors (sleep) | 0.7 (−0.6 to 2.1) | −0.4 (−1.8 to 0.9) | 1.1 (−0.7 to 3.0) | 0.43 | t(63)=1.19,0.24 |
| NPI appetite | 0.6 (−0.5 to 1.6) | 0.6 (−0.5 to 1.6) | 0.0 (−1.4 to 1.5) | 0.00 | t(63)=0.00, 1.00 |
| BADL | 0.3 (−0.1 to 0.7) | 0.1 (−0.3 to 0.6) | 0.2 (−0.4 to 0.8) | 0.18 | t(59)=0.49,0.63 |
| YMRS | 3.1 (0.9 to 5.3) | 1.1 (−1.1 to 3.3) | 2.0 (−1.1 to 5.1) | 0.46 | t(62)=1.28,0.21 |
| Zarit Caregiver Burden | 2.8 (−1.1 to 6.6) | −0.4 (−4.2 to 3.3) | 3.2 (−2.1 to 8.4) | 0.44 | t(58)=1.19,0.24 |
| Safety Outcomes | |||||
| TESS | 0.6 (−1.3 to 2.4) | 0.7 (−1.1 to 2.5) | −0.1 (−2.6 to 2.4) | −0.04 | t(62)=−0.11,0.91 |
| Simpson-Angus Scale | −0.0 (−1.1 to 1.0) | 0.0 (−1.0 to 1.0) | 0.1 (−1.5 to 1.4) | −0.02 | t(62)=−0.07,0.94 |
| Get Up and Go Time | 3.5 (−2.6 to 9.5) | 0.6 (−5.5 to 6.7) | 2.9 (−5.6 to 11.3) | 0.24 | t(65)=0.67,0.50 |
| MMSE | 0.9 (−0.3 to 2.2) | 0.9 (−0.4 to 2.1) | 0.0 (−1.7 to 1.8) | 0.01 | t(57)=0.05,0.96 |
| SIB | 2.1 (−1.1 to 5.4) | −0.0 (−3.3 to 3.2) | 2.2 (−2.3 to 6.6) | 0.35 | t(56)=0.94,0.35 |
| Change in Creatinine week 0: | |||||
| to week 6, abnormal (%) | 2/35 (5.7) | 1/33 (3) | 1.94 0.17–22.46)2 | - | 13 |
| to week 12, abnormal (%) | 0/29 (0) | 0/28 (0) | NA4 | - | ㅡ |
| Change in eGFR from week 0 | |||||
| to week 6, abnormal (%) | 3/35 (8.6) | 2/33 (6.1) | 1.45 (0.15 to 18.40)2 | - | 13 |
| to week 12, abnormal (%) | 1/29 (3.4) | 1/28 (3.6) | 0.96 0.06 to 16.21)2 | - | 13 |
Linear mixed effect models were used to estimate means of change scores by treatment group, lithium versus placebo, for continuous outcomes.
CGI: Clinical Global Impression: range 1–7 (higher scores indicate greater severity). NPI: Neuropsychiatric Inventory: range 0–144 (higher score indicates greater symptoms). NPI domain (agitation/aggression, hallucinations, delusions, depression, anxiety, elation, disinhibition, irritability, lability, aberrant motor behavior, apathy, nighttime behavior (sleep), appetite): range 0–12 (higher scores indicate greater symptoms). NPI psychosis (sum of scores for NPI domains: delusions and hallucinations): range 0–24 (higher score indicates greater symptoms). NPI core score (sum of scores for NPI domains: agitation/aggression, delusions, and hallucinations): range 0–36 (higher score indicates greater symptoms). Basic Activities of Daily Living: range 0–6 (higher scores indicate better functioning). Young Mania Rating Scale: range 0–60 (higher scores indicate greater symptoms). Zarit Caregiver Burden Interview: range 0–88 (higher scores indicate greater burden). Treatment Emergent Symptom Scale: range 0–26 (higher scores indicate more somatic symptoms). Simpson Angus Scale for Extrapyramidal Signs: range 0–40 (higher scores indicate increased severity of signs). Mini Mental State Exam: range 0–30 (higher scores indicate better cognition). Severe Impairment Battery: range 0–100 (higher scores indicate better cognition). eGFR: estimated Glomerular Filtration Rate: range 0–60 (higher scores indicate better kidney function).
Cohen’s d for continuous variables.
Odds ratio (OR) for categorical variables. CGI change measures for behavior and global classified as 1 or 2 (much/very much improved) versus 3–7 (mildly improved to very much worse). Chi-square test was used.
Fisher’s exact test used because of cells with low frequency.
OR was not computed due to a zero cell.